The present invention relates to an improved process for the production of 4-hydroxyphenethyl alcohol, or more particularly to a method of producing 4-hydroxyphenethyl alcohol from 4-acetoxystyrene.
4-Hydroxyphenethyl alcohol is useful as an intermediate in the preparation of pharmaceutical compounds. It is known from U.S. Pat. No. 4,760,182 that 4-hydroxyphenethyl alcohol may be used to prepare phenoxypropanolamines, in particular the beta-adrenergic blocking agent betaxolol. It is also described in EP patent application 249 245 that it can find use as an intermediate in the preparation of the antihypertensive agents phenyl (dialkyl)dihydro- pyridinedicarboxylates. As taught in JP 86-201940 it is also useful in the preparation of (aminopropoxyphenyl) alkanols and esters which are employed in the treatment of glaucoma. From the foregoing discussion it is clear that 4-hydroxyphenyl alcohol is a well known compound and in fact, it has been produced by a variety of methods. Yamada et al, Chem. Pharm. Bull. (Tokyo) 11, 258-60 (1963) suggests one method of its preparation from the corresponding amine, which however is not readily accessible. Khafagy et al, J. Med. Chem (1966) 9 (6), 936 prepare p-hydroxyphenethyl alcohol by converting 4-hydroxyphenyl acetic acid to its ethyl ester and subsequent conversion to its acetoxy derivative. The acetoxyethyl ester is then reduced with lithium aluminum hydride and then finally saponified to give 4-hydroxyphenethyl alcohol. Hussein, Angew. Botan., 38(1), 1-43 (1964) prepares p-hydroxyphenethyl alcohol in a sequence of oxidation and reduction steps from phenethyl alcohol. He additionally reports the extraction of p-hydroxyphenethyl alcohol from certain tree barks.
It has now been found that 4-hydroxyphenethyl alcohol can be prepared in yields of about 96% or more and with a high purity of about 99% or more. The process involves epoxidizing 4-acetoxystyrene, catalytically hydrogenating the resulting oxirane and saponifying or transesterifying the intermediate acetoxyphenethyl alcohol.